Alzheimer’s Disease: Type III Diabetes in Disguise?

Authored By: Lauren Wilkes

Art By: Carla Hu

What does the phrase “impaired cognitive function” tell us about Alzheimer’s Disease? Does the notion of severe “memory loss” or even a clinical classification of “dementia,” adequately explain the biochemical underpinnings of Alzheimer’s Disease (AD)? Alzheimer’s Disease is generally classified as a type of dementia that affects memory, thinking, and behavior [1] and is most commonly diagnosed when it is visibly detectable in the patient [2]. Unfortunately, progression is relatively far along at that point. Although the patient may have just begun exhibiting Alzheimer's symptoms, in reality, Alzheimer’s Disease was present, biologically, from the “preclinical” stage [2]. 

One of the reasons for the lack of preclinical detection is the lack of research regarding the surrounding biochemical factors potentially contributing to Alzheimer’s Disease. However, recent research has displayed a strong connection between poorly controlled insulin and the development of Alzheimer's Disease [3]. Insulin is most commonly known as a hormone that regulates blood sugar, but it is also a vital hormone for brain function maintenance. Insulin is an integral facet of brain health and function because insulin signaling in the brain is largely responsible for regulating the function of neuronal and glial cells within the brain, thereby impacting brain cognition and behavior [4]. The question, however, beyond this connection, remains that, although insulin and blood sugar regulation in Type 2 Diabetes may correlate with Alzheimer's, what role does insulin play in the brain that influences Alzheimer's? 

Insulin resistance in the brain can introduce numerous neurotoxins that can prevent the necessary aforementioned functions, as well as many others. Evidence in recent years has come to demonstrate that there is partial local insulin secretion in the brain by the central nervous system (CNS). Furthermore, insulin aids in regulating glucose metabolism in the brain which is, in fact, vital in our potential to identify the onset of Alzheimer’s much earlier on. This stems from the fact that, as seen in a study published in the International Journal of Molecular Science and NCBI on “How Insulin Resistance Causes Alzheimer’s Disease,” [5] when looking at the correct biological markers – namely glucose metabolism in this context – we can identify potentially very strong indicators of Alzheimer’s, even at the beginning of the preclinical stage. It is evident, according to NCBI, that based on recent findings, a “decrease in brain glucose metabolism occurs more than 10 years before the onset of AD symptoms.” [5].  

Moreover, the hippocampus, the epicenter of learning and memory, has insulin receptors pervading its domain. Insulin receptors act as vital transmembrane proteins in the brain which bind to insulin [6]. In the context of diabetes and AD, the higher the degree of insulin resistance, the less insulin receptors present, and in the brain, when insulin receptors are no longer present throughout the domain that regulates memory function (the hippocampus), the patients’ memory is bound to decline. This, however, is a very subcellular, biochemical cascade and is not always producing visible symptoms immediately, thus explaining the notion that when we diagnose the onset of Alzheimer's it is, in reality, very far along. Thus, it is imperative that we utilize this deepening knowledge of the correlation to aid in reclassifying how we approach the disease to aid in more premature diagnoses [7]. 

For these reasons, it seems clear that Alzheimer's and insulin resistance in the brain are highly linked. As a result, insulin resistance in the brain has very recently started to be termed “Type III Diabetes.” Furthermore, NCBI states that, “globally, the incidence of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) epidemics is increasing rapidly,” and according to relevant statistics per a study done by the American Diabetes Association, 32% of Alzheimer’s patients also had Type II Diabetes, as opposed to the 14% of non-Alzheimer’s patients [8]. This data continues to corroborate the notion that there is an established link between diabetes and AD that play a significant role in the development and causation of Alzheimer’s Disease [9]. 

The reclassification of Alzheimer’s Disease as Type III Diabetes offers a more clear pathway for treatment. This recategorization could provide a more foundational, supported, and informed approach to Alzheimer’s treatment, leveraging existing knowledge about treatment. However, some of the medical community feel that classifying Alzheimer’s as or in the context of Type III Diabetes, is an oversimplification. On the other hand, classifying Alzheimer’s Disease as memory loss and impaired cognitive function can be limiting as clinicians may prevent themselves from making earlier prognoses. Given current diagnoses are made when the patient is too far along (i.e. even just beginning to exhibit symptoms), so much of the battle against Alzheimer’s Disease comes from earlier diagnoses. With a reconsideration of Alzheimer's, the dream of premature diagnosis is no longer out of reach. If we can use this perspective to achieve more clarity on the disease and transform the lives of even one patient, a new consideration of Alzheimer’s as Type III Diabetes is more than worth it. 

References

1. Alzheimer's Association. (2024). What is Alzheimer’s Disease? Alzheimer’s Disease and Dementia; Alzheimer’s Association. https://www.alz.org/alzheimers-dementia/what-is-alzheimers 

2. Detect mild cognitive impairment before clinical symptoms. Learn how. (n.d.). https://www.youngerthanyouthink.com/mci-due-to-ad?utm_source=google&utm_medium=cpc&utm_campaign=Condition+Education%3BS%3BPH%3BUB%3BNER%3BHCP%3BCON&utm_term=early+indicators+of+alzheimers&utm_content=Symptoms_Phrase&gclsrc=aw.ds&&gclid=CjwKCAjwmaO4BhAhEiwA5p4YL0iQTWERulm7-AgCxbJ6HotpaOhjQpfG3VY8LsnvpFsCjP4MLvRHDBoCwIoQAvD_BwE&gad_source=1 

3. Nguyen, T. T., Ta, Q. T. H., Nguyen, T. K. O., Nguyen, T. T. D., & Giau, V. V. (2020). Type 3 Diabetes and Its Role Implications in Alzheimer's Disease. International journal of molecular sciences, 21(9), 3165. https://doi.org/10.3390/ijms21093165  

4. Chen, W., Cai, W., Hoover, B., & Kahn, C. R. (2022). Insulin action in the brain: cell types, circuits, and diseases. Trends in Neurosciences, 45(5), 384–400. https://doi.org/10.1016/j.tins.2022.03.001 

5. Yoon, J. H., Hwang, J., Son, S. U., Choi, J., You, S. W., Park, H., Cha, S. Y., & Maeng, S. (2023). How Can Insulin Resistance Cause Alzheimer's Disease?. International journal of molecular sciences, 24(4), 3506. https://doi.org/10.3390/ijms24043506

6. Lee, J., & Pilch, P. F. (1994). The insulin receptor: structure, function, and signaling. The American journal of physiology, 266(2 Pt 1), C319–C334. https://doi.org/10.1152/ajpcell.1994.266.2.C319 

7. Liu, Q., Wang, Z., Cao, J., Dong, Y., & Chen, Y. (2022). The Role of Insulin Signaling in Hippocampal-Related Diseases: A Focus on Alzheimer's Disease. International journal of molecular sciences, 23(22), 14417. https://doi.org/10.3390/ijms232214417 

8. Michailidis, M., Moraitou, D., Tata, D. A., Kalinderi, K., Papamitsou, T., & Papaliagkas, V. (2022). Alzheimer's Disease as Type 3 Diabetes: Common Pathophysiological Mechanisms between Alzheimer's Disease and Type 2 Diabetes. International journal of molecular sciences, 23(5), 2687. https://doi.org/10.3390/ijms23052687 

9. Janson, J., Laedtke, T., Parisi, J. E., O'Brien, P., Petersen, R. C., & Butler, P. C. (2004). Increased risk of type 2 diabetes in Alzheimer disease. Diabetes, 53(2), 474–481. https://doi.org/10.2337/diabetes.53.2.474